Upfront triple combination therapy in severe paediatric pulmonary arterial hypertension

INTRODUCTION: Treatment strategies in paediatric pulmonary arterial hypertension (PAH) have evolved over the last years, but survival is still poor. Recently, in adults with severe PAH, upfront triple combination therapy (uTCT) from diagnosis has been reported to show significant clinical improvement and excellent long-term outcome. This retrospective, observational study aimed to assess the efficacy of uTCT in paediatric PAH. METHODS: Children diagnosed with PAH between 2010 and 2019 and started with uTCT were included. World Health Organization Functional Class (WHO-FC), haemodynamics, echocardiography, six-minute walking distance, and serum level of N-terminal-Pro-Brain-Natriuretic-Peptide were assessed at baseline, after three and 6 months and at last available follow-up. Events were defined as death, lung transplantation or Potts shunt. RESULTS: Twenty-one children (median age 4.8 years (2.5-12.8), 57% females) were included. All children except one were in WHO-FC III or IV (28% and 67%, respectively). After 3 months, one child had died and one child had received a Potts shunt. The remaining 19 children showed clinical and echocardiographic improvement, which persisted at 6 months. Children with idiopathic and heritable PAH showed one-, two-, and three-year transplant-free survival estimates of 100%, 94%, and 87%, albeit 47% of them receiving a Potts shunt during follow-up. CONCLUSIONS: Children with severe PAH, but not pulmonary veno-occlusive disease, improved significantly with uTCT and showed beneficial up to 3-year survival rates, albeit 47% of them receiving a Potts shunt during follow-up. The role of a Potts shunt in conjunction to uTCT in paediatric PAH needs to be further established

282: Distribution of causes and outcomes of pulmonary hypertensions in a tertiary pediatric hospital

ObjectivesTo describe the distribution of causes of pediatric pulmonary hypertension (PH) based on the experience of a pediatric PH department in a tertiary hospital with pluridisciplinary approach including rare diseases.BackgroundThe causes of PH have been well characterized in adult and pediatric large registries but the type of PH seen in expert centers has been modified by improved screening and diagnosis strategies.MethodsBetween 2008 and 2010, all PH patients referred to our PH department were included in a PH data base and classified according to the Dana Point clinical classification. Clinical, hemodynamic features, and outcomes of the first 212 cases are described.ResultsThe median age at diagnosis of PH was 2.4 years (range 0.4–15); 56% were girls. At diagnosis, 40% of the patients were in functional class III or IV. Mean pulmonary artery pressure at diagnosis was 54.6±16.6mmHg, PVR was 16±7 Wood Unit and cardiac index 3.2±0.8l/min/m2. Of 212 cases, 160 (75%) were in group 1 pulmonary arterial hypertension (PAH): idiopathic or heritable in 38 children and, associated with congenital heart disease (CHD) in 122 (57.5%). Six children were in group 2 PH (left heart disease), 30 (14%) were in group 3 PH (8 diaphragmatic hernias, 13 bronchopulmonary dysplasias, 5 interstitial lung diseases, 4 other causes), no children of our series were in group 4 PH, and finally 16 out of the 122 (7.5%) were included in group 5. At last follow-up, 93% of the PAH patients had received PAH specific drugs, and overall 85% of patients remained in a stable condition. Survival after three years follow-up was 94%,ConclusionThe spectrum of causes, diagnostic challenges and gender distribution of pediatric PH in our national pediatric PH expert center are different to that in adults but also to that described in large pediatric registries. Still, clinical classification of PH appears appropriate in pediatrics. Our study also highlights current management and shows an improved prognosis with more aggressive therapeutic option

Arterial stiffness and endothelial dysfunction in HIV-infected children

The role of antiretroviral therapy in acceleration of atherosclerosis in HIV-infected adults is controversial, partly because of the confounding effects of the involvement of classic cardiovascular risk factors

Safety, efficacy and Management of subcutaneous treprostinil infusions in the treatment of severe pediatric pulmonary hypertension

International audienceThe prevalence of germline mutations in paediatric pulmonary hypertension (PH) is poorly documented. The objective of this study was to determine the mutation frequency in PH genes in a paediatric cohort and describe the clinical characteristics of mutation carriers. The study involved 66 index cases with PH: 35 children with idiopathic pulmonary arterial hypertension (IPAH); five children with familial PAH (FPAH); three children with pulmonary veno-occlusive disease (PVOD); and 23 children with PAH associated with congenital heart disease (APAH-CHD). No mutations were found in the 23 children with APAH-CHD. In the 40 children with IPAH or FPAH, 12 mutations were found: five on BMPR2 ; four on ACVRL1 ; and three on TBX4. In the three PVOD cases, two carried the EIF2AK4 mutation. Mutation carriers had a more severe disease at diagnosis and more aggressive first-line therapy was required. The three patients with PVOD had a very severe disease at diagnosis and required a lung transplantation. The genetic architecture of paediatric PAH is enriched in ACVRL1 and TBX4 mutations compared to adult PAH, but further studies are required to confirm these results. Childhood-onset PAH in children carrying a mutation in one of the genes tested has a more severe presentation at diagnosis but a similar outcome to that observed in non-carriers

Monitoring of Hemodynamics With Right Heart Catheterization in Children With Pulmonary Arterial Hypertension

Background Right heart catheterization (RHC) is a high‐risk procedure in children with pulmonary arterial hypertension without clear guidelines for the indications and targets of invasive reassessment. Our objectives are to define the aims of repeated RHC and evaluate the correlation between noninvasive criteria and hemodynamic parameters. Methods and Results Clinical and hemodynamic characteristics from 71 incident treatment‐naïve children (median age 6.2 years) with pulmonary arterial hypertension who had a baseline and reevaluation RHC were analyzed. Correlations between noninvasive predictors and hemodynamic parameters were tested. Adverse outcomes were defined as death, lung transplantation, or Potts shunt. At baseline, pulmonary vascular resistance index (hazard ratio [HR] 1.07 per 1 WU·m2 increase [95% CI, 1.02–1.12], P=0.002), stroke volume index (HR 0.95 per 1 L·min−1·m−2 increase [95% CI, 0.91–0.99], P=0.012), pulmonary artery compliance index (HR 0.16 per 1 mL·mm Hg−1·m−2 increase [95% CI, 0.051–0.52], P=0.002), and right atrial pressure (HR, 1.31 per 1 mm Hg increase [95% CI, 1.01–1.71], P=0.043) were associated with adverse outcomes. Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure were still associated with a worse outcome at second RHC. Noninvasive criteria accurately predicted hemodynamic evolution; however, 70% of the patients who had improved based on noninvasive criteria still presented at least 1 “at risk” hemodynamics at second RHC. Conclusions Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure are solid predictors of adverse outcomes in pediatric pulmonary arterial hypertension and potential therapeutic targets. Noninvasive criteria accurately predict the evolution of hemodynamic parameters, but insufficiently. Repeated RHC are helpful to identify children with persistent higher risk after treatment introduction

Vascular remodeling after "successful" repair of coarctation: impact of aortic arch geometry.

OBJECTIVES: This study was designed to investigate the influence of aortic arch geometry on vascular remodeling after anatomically successful repair of coarctation of the aorta (CoA). BACKGROUND: Abnormalities of the precoarctation vasculature are known to occur after CoA repair and appear related to adverse outcomes. The influence of aortic arch geometry on such abnormalities is unknown. METHODS: Sixty-three postcoarctectomy subjects (age 15.9 +/- 6.3 years) were compared with 63 control volunteers. Aortic arch shape was characterized on magnetic resonance imaging using both qualitative classification, identifying 3 subtypes of arch geometry (Gothic, Crenel, Romanesque), and a quantitative index, height/width ratio (H/W) of the aorta. Using ultrasound, we measured carotid artery intima-media thickness (IMT) and stiffness index and distensibility, as well as right brachial artery flow-mediated dilation (FMD) and glyceryl trinitate (GTN)-induced dilatation, to assess the precoarctation vasculature of these subjects. RESULTS: Gothic arch type was associated with higher carotid IMT and stiffness index, lower carotid distensibility (p < 0.001 for all), and lower brachial reactivity (FMD, p < 0.01; GTN response, p < 0.001) compared with Crenel and Romanesque geometries and with control subjects. The height/width ratio was also significantly related to these vascular abnormalities. Even in CoA subjects with Romanesque arch geometry, arterial function and stiffness parameters were significantly impaired compared with control subjects. CONCLUSIONS: In young adult survivors of anatomically successful CoA repair, a gothic-type aortic arch with high H/W is associated with abnormal IMT, higher aortic stiffness index, and impaired arterial reactivity in the pre-CoA vasculature